The broad objective of this proposal is to investigate the possible causes of the mucous abnormality in Cystic Fibrosis. The potential pathogenetic contribution of disturbances in the neurohumoral regulation of pulmonary secretions will be evaluated by studying the role of neurohumoral mediators in regulating the structural, histochemical and functional characteristics of the mucous-producing elements of the respiratory tree. These studies will be carried out in an experimental animal model that has been developed in our laboratory and will include both light and electron microscopic analysis of the structural characteristics of airways and the assessment of the organic and inorganic composition of pulmonary secretions. The effects of autonomic secretagogues and their antagonists on the morphology and secretory capacity of the mucus elements of the respiratory tree will be studied by means of acute and chronic modes of treatment with appropriate drugs. Results from these studies in the animal model will be correlated with observations in Cystic Fibrosis patients. For this purpose, the cytochemistry and ultrastructure of the respiratory epithelium and chemistry of secretions will be studied in relation to the onset and clinical course of respiratory disease and also to the modes and extent of therapeutic measures.